A patient with type 2 diabetes is usually treated by giving a patient education for improving a life style such as a diet therapy or exercise therapy, medication including administration of an oral hypoglycemic agent or insulin, or a combination thereof.
As an oral hypoglycemic agent, an insulin secretagogue such as a sulfonylurea-based medicine, a sugar absorption regulator such as an α-glucosidase inhibitor, an insulin resistance improving agent such as a thiazolidine-based medicine or a biguanide-based medicine, or the like is used corresponding to a condition of the patient.
Recently, a rapid-acting insulin secretagogue such as nateglinide, repaglinide, mitiglinide calcium hydrate (product name: Glufast (registered trademark)) or the like, which is a kind of the oral hypoglycemic agent, has been proposed and received attention since a significant therapeutic effect thereof on improvement of a course of postprandial blood glucose has been shown. In a patient with type 2 diabetes, an increase in early-phase of insulin secretion after sugar loading, especially the increase within 30 minutes after the sugar loading is known to be significantly smaller than that of a healthy person. That is, while a blood glucose level of a healthy person gradually increases for 30 to 60 minutes after loading of glucose and then slowly decreases, when glucose is loaded to a patient with type 2 diabetes, a phenomenon of a precipitous increase in a blood glucose level within 30 to 90 minutes, which is called “glucose spike”, is observed, because of low insulin secretion capability (Mebio, May 2003, Supplement “SYOKUGO KOUKETTO/IGT TO DAIKEKKANSYOUGAI (Postprandial Hyperglycemia/IGT and Macroangiopathy)” pp. 26-37). Therefore, a preferable drug exhibits efficacy in an early period after meal, especially within 30 to 60 minutes, to make a blood glucose course similar to that of a healthy person. The rapid-acting insulin secretagogue, particularly mitiglinide calcium hydrate is known to show a significant effect on improvement of a course of postprandial blood glucose. Mitiglinide calcium hydrate, however, is not known to effectively suppress glucose spike, especially glucose spike occurring within 1 hour after meal.
On the other hand, a combination therapy including administration of a combination of various drugs has been attempted to improve conditions of diabetes. As an example, a combined pharmaceutical including a combination of an α-glucosidase inhibitor and a non-sulfonylurea-based insulin secretagogue has been reported (Japanese Patent Publication No. 2001-316293). This report, however, does not describe specific effects of a combination of mitiglinide calcium hydrate and an α-glucosidase inhibitor, such as an extremely strong synergistic effect of decreasing a morning fasting blood glucose level, a postprandial blood glucose level and HbA1C, suppression of glucose spike, and an effect of improving insulin resistance and lipid metabolism, as well as safety of the combination therapy, and the like.
In addition, a combination therapy of nateglinide and an α-glucosidase inhibitor has been reported to reproduce a blood glucose response comparable to that of a healthy person (Ryuzo Kawamori, “NAIBUNPI TONYOBYOKA (Endocrinology & Diabetology)”, 12(6): 574-578, 2001). This report, however, does not include a detailed comparison between a monotherapy of nateglinide or the α-glucosidase inhibitor and the combination therapy, and there is no description regarding or suggesting the specific effects of combination as described above.